Global Patent Index - EP 2119717 A1

EP 2119717 A1 20091118 - 8-[3-amino-piperidin-1-yl]-xanthins, their production and utilisation as DPP IV inhibitors

Title (en)

8-[3-amino-piperidin-1-yl]-xanthins, their production and utilisation as DPP IV inhibitors

Title (de)

8-[3-amino-piperidin-1-yl]-Xanthine, deren Herstellung und deren Verwendung als DPP IV Hemmer

Title (fr)

8-[3-amino-pipéridine-1-yl]-xanthine, leur fabrication et leur utilisation en tant que complexe DDP IV

Publication

EP 2119717 A1 20091118 (DE)

Application

EP 09158875 A 20050212

Previously filed application

05707354 20050212 EP

Priority

  • EP 05707354 A 20050212
  • DE 102004008112 A 20040218
  • DE 102004012921 A 20040317
  • DE 102004032263 A 20040703

Abstract (en)

7-Butynyl-8-(3-amino-1-piperidinyl)xanthine derivatives (I) are new. 7-Butynyl-8-(3-amino-1-piperidinyl)xanthine derivatives of formula (I) and their tautomers, isomers and salts are new. R : benzyl, 2-fluorobenzyl, 3-fluorobenzyl, 4-fluorobenzyl, 2,6-difluoro-benzyl, 3,4-difluoro-benzyl, 2-chlorobenzyl, 3-chlorobenzyl or 4-chlorobenzyl, 2-trifluoromethyl-benzyl, 3-trifluoromethyl-benzyl or 4-trifluoromethyl-benzyl, 3-trifluoromethoxy-benzyl or 4-trifluoromethoxy-benzyl, 2-cyanobenzyl, 3-cyanobenzyl or 4-cyanobenzyl, 2,6-dicyanobenzyl, 3,4-dicyanobenzyl, 3,5-dicyanobenzyl, 2-trifluoromethyl-4-cyano-benzyl, 3-nitro-4-cyano-benzyl, 2-cyano-3-methoxy-benzyl, 2-cyano-4-methoxy-benzyl, 2-cyano-5-methoxy-benzyl, 2-cyano-4-fluoro-benzyl, 2-cyano-5-fluoro-benzyl, 2-cyano-6-fluoro-benzyl, 3-cyano-4-fluoro-benzyl, 4-cyano-3-fluorobenzyl, 2-fluoro-4-cyano-benzyl, 2-cyano-3-chlorobenzyl, 2-chloro-4-cyano-benzyl or 2-cyano-4-bromobenzyl, 2-methoxy-benzyl, 3-methoxy-benzyl, 4-methoxy-benzyl, 2-fluoro-3-methoxybenzyl, 2-fluoro-4-methoxy-benzyl, 2-fluoro-5-methoxy-benzyl, 3-fluoro-4-methoxybenzyl, 3,4-dimethoxy-benzyl, 3,5-dimethoxybenzyl or 3,4-dimethoxy-6-fluorobenzyl, (benzo[1,3]dioxol-5-yl)methyl, [(4-cyano-benzo[1,3]dioxol-5-yl)methyl, 2-(3-cyclopropyloxy-phenyl)-2-oxo-ethyl, 2-(3-cyclopropylmethoxy-phenyl)-2oxo-ethyl or 2-(3-cyclobutyloxy-phenyl)-2-oxo-ethyl, 2-oxo-2-[2-(pyridin-3-yl)-phenyl]-ethyl or 2-oxo-2-[2-(pyridin-4-yl)-phenyl]ethyl, (3-cyano-1-naphthyl)methyl, (1,4-dicyano-2-naphthyl)methyl or (2,4-dimethoxy-1-naphthyl)methyl, (furan-2-yl)methyl, (furan-3-yl)methyl, (5-bromo-furan-2-yl)methyl, (5-methylfuran-2-yl)methyl, (5-cyano-furan-2-yl)methyl or (5-methoxycarbonyl-furan-2yl)methyl, (pyridin-2-yl)methyl, (6-fluoro-pyridin-2-yl)methyl or (5-methoxy-pyridin-2-yl)methyl, (3-cyanopyridin-2-yl)methyl, (6-cyanopyridin-2- yl)methyl, (5-cyano-pyridin-2-yl)methyl, (4-cyano-pyridin-2-yl)methyl, (4-cyano-pyridin-3-yl)methyl, (3-cyanopyridin-4-yl)methyl, (2-cyano-pyridin-3-yl)methyl, (2-cyano-pyridin-4-yl)methyl, (5cyano-pyridin-3-yl)methyl, (6-cyano-pyridin-3-yl)methyl or (5-cyano-6-methoxypyridin-2-yl)methyl, (6-phenyl-pyridin-2-yl)methyl or ([2,2']bipyridinyl-6-yl)methyl, (pyrimidin-2-yl)methyl, (4-methyl-pyrimidin-2-yl)methyl or (4,6-dimethylpyrimidin-2-yl)methyl, (2-phenyl-pyrimidin-4-yl)methyl or (4-phenyl-pyrimidin-2-yl)methyl, [(1-methyl-1H-benzotriazol-5-yl)methyl], (6-fluoro-quinolin-2-yl)methyl, (7-fluoro-quinolin-2-yl)methyl, (2-methyl-quinolin-4-yl)methyl, (3-cyano-quinolin-2-yl)methyl, (3-cyano-4-methyl-quinolin-2-yl)methyl, (4-cyano-quinolin-2-yl)methyl, (5-cyano-quinolin-2-yl)methyl, (6-cyano-quinolin-2-yl)methyl, (6-amino-quinolin-2-yl)methyl, (8-amino-quinolin-2-y1)methyl, (4-methoxy-quinolin-2-yl)methyl, (6-methoxy-quinolin-2-yl)methyl, (6,7-dimethoxyquinolin-2-yl)methyl or (8-cyano-quinolin-7-yl)methyl, (1-cyano-isoquinolin-3-yl)methyl, (4-cyano-isoquinolin-1-yl)methyl, (4-cyanoisoquinolin-3-yl)methyl or [(4-(pyridin-2-yl)-isoquinolin-1-yl)methyl, (quinazolin-6-yl)methyl, (quinazolin-7-yl)methyl, (2-methyl-quinazolin-4yl)methyl, (4,5-dimethyl-quinazolin-2-yl)methyl, (4-ethyl-quinazolin-2-yl)methyl, (4-cyclopropyl-quinazolin-2-yl)methyl, (2-phenyl-quinazolin-4-yl)methyl, (4-cyanoquinazolin-2-yl)methyl, (4-phenylamino-quinazolin-2-yl)methyl or (4-benzylaminoquinazolin-2-yl)methyl, (quinoxalin-5-yl)methyl, (quinoxalin-6-yl)methyl or (2,3-dimethyl-quinoxalin-6-yl)methyl, or ([1,5]naphthyridin-3-yl)methyl. An independent claim is also included for a process for preparing (I). [Image] ACTIVITY : Antidiabetic; Antiarthritic; Anorectic; Osteopathic; Tranquilizer; Hypotensive; Nephrotropic; Antiinflammatory; Antiulcer; Immunosuppressive; Virucide; Anti-HIV; Neuroprotective; Nootropic; Cytostatic; Cerebroprotective; Vasotropic; Antiparkinsonian; Antimigraine; Dermatological; Antipsoriatic; Antidepressant; Neuroleptic. MECHANISM OF ACTION : Dipeptidyl peptidase IV (DPP IV) inhibitor. 1-(4-Benzylamino-4-quinazolinylmethyl)-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-1-piperidinyl)xanthine had an IC50 of 6 nM against DPP IV activity in Caco-2 cell extracts.

Abstract (de)

Die vorliegende Erfindung betrifft substituierte Xanthine der allgemeinen Formel in der R wie in Anspruch 1 definiert sind, deren Tautomere, deren Stereoisomere, deren Gemische und deren Salze, welche wertvolle pharmakologische Eigenschaften aufweisen, insbesondere eine Hemmwirkung auf die Aktivität des Enzyms Dipeptidylpeptidase-IV (DPP-IV).

IPC 8 full level

C07D 473/04 (2006.01); A61K 31/437 (2006.01); A61P 3/10 (2006.01)

CPC (source: EP KR)

A61K 31/44 (2013.01 - KR); A61P 1/02 (2017.12 - EP); A61P 1/04 (2017.12 - EP); A61P 1/18 (2017.12 - EP); A61P 3/00 (2017.12 - EP); A61P 3/04 (2017.12 - EP); A61P 3/10 (2017.12 - EP); A61P 5/00 (2017.12 - EP); A61P 5/02 (2017.12 - EP); A61P 7/10 (2017.12 - EP); A61P 9/10 (2017.12 - EP); A61P 9/12 (2017.12 - EP); A61P 13/08 (2017.12 - EP); A61P 13/12 (2017.12 - EP); A61P 15/08 (2017.12 - EP); A61P 15/16 (2017.12 - EP); A61P 17/00 (2017.12 - EP); A61P 17/06 (2017.12 - EP); A61P 19/02 (2017.12 - EP); A61P 19/10 (2017.12 - EP); A61P 25/00 (2017.12 - EP); A61P 25/06 (2017.12 - EP); A61P 25/16 (2017.12 - EP); A61P 25/24 (2017.12 - EP); A61P 25/28 (2017.12 - EP); A61P 29/00 (2017.12 - EP); A61P 31/12 (2017.12 - EP); A61P 31/18 (2017.12 - EP); A61P 35/00 (2017.12 - EP); A61P 35/02 (2017.12 - EP); A61P 35/04 (2017.12 - EP); A61P 37/06 (2017.12 - EP); A61P 43/00 (2017.12 - EP); C07D 473/04 (2013.01 - EP KR); C07D 473/06 (2013.01 - KR)

Citation (applicant)

Citation (search report)

Designated contracting state (EPC)

AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IS IT LI LT LU MC NL PL PT RO SE SI SK TR

DOCDB simple family (publication)

WO 2005085246 A1 20050915; AR 047614 A1 20060125; AT E430150 T1 20090515; AU 2005219508 A1 20050915; AU 2005219508 B2 20120216; BR PI0507873 A 20070724; BR PI0507873 B1 20180925; BR PI0507873 B8 20210525; CA 2555050 A1 20050915; CA 2555050 C 20171128; CN 102199151 A 20110928; CY 1109284 T1 20140702; DE 502005007196 D1 20090610; DK 1758905 T3 20090824; EA 010854 B1 20081230; EA 200601496 A1 20070227; EA 200801601 A1 20090828; EC SP066775 A 20061116; EP 1758905 A1 20070307; EP 1758905 B1 20090429; EP 2119717 A1 20091118; EP 2119717 B1 20180117; ES 2326666 T3 20091016; HK 1103402 A1 20071221; HR P20090346 T1 20090831; IL 176920 A0 20061210; IL 176920 A 20120329; IL 217268 A0 20120229; JP 2007522251 A 20070809; JP 2011006437 A 20110113; JP 4733058 B2 20110727; KR 101207224 B1 20121203; KR 20070006780 A 20070111; ME 01108 B 20130320; MY 144322 A 20110829; NO 20062688 L 20060914; NZ 548901 A 20100827; PE 20060210 A1 20060410; PL 1758905 T3 20091030; PT 1758905 E 20090716; RS 50982 B 20101031; SI 1758905 T1 20091031; TW 200538131 A 20051201; TW I350756 B 20111021; UY 28749 A1 20050930

DOCDB simple family (application)

EP 2005001427 W 20050212; AR P050100578 A 20050218; AT 05707354 T 20050212; AU 2005219508 A 20050212; BR PI0507873 A 20050212; CA 2555050 A 20050212; CN 201110084216 A 20050212; CY 091100791 T 20090723; DE 502005007196 T 20050212; DK 05707354 T 20050212; EA 200601496 A 20050212; EA 200801601 A 20050212; EC SP066775 A 20060818; EP 05707354 A 20050212; EP 09158875 A 20050212; ES 05707354 T 20050212; HK 07111729 A 20071031; HR P20090346 T 20090615; IL 17692006 A 20060718; IL 21726811 A 20111229; JP 2006553504 A 20050212; JP 2010178510 A 20100809; KR 20067019124 A 20060918; ME P23509 A 20050212; MY PI20050575 A 20050216; NO 20062688 A 20060609; NZ 54890105 A 20050212; PE 2005000183 A 20050216; PL 05707354 T 20050212; PT 05707354 T 20050212; RS P20090303 A 20050212; SI 200530736 T 20050212; TW 94104568 A 20050217; UY 28749 A 20050215